Figure 2 - uploaded by Maria Sokolova
Content may be subject to copyright.
Actin Colocalizes with Pol II at TSS and Gene Bodies of Transcribed Genes (A) Heatmap of the ratio between the sample (histone H3K4met3, Pol II S5P, and actin with two antibodies, AC-74 and AC15) and input ChIP-seq signals across gene regions, standardized and segmented into 200 bins. Transcription start sites (TSS) and transcription end sites (TES) are indicated. Genes are sorted according to normalized read count (NRC) of RNA sequencing data from w 1118 fly ovaries (right panel). (B) Venn diagram showing overlap of actin (AC-74) and Pol II S5P peaks from ChIP-seq. (C) Average signal of read counts normalized to the input from À500 bp to +500 bp from the TSS of gene loci (n = 10,843). (D and E) (D) Binding profile of actin and Pol II on chorion genes at 66D locus of chromosome 3L. Antibodies used in ChIPseq are indicated on the left, and signal intensity as number of reads is shown in parentheses above each track. Results from two experiment replicates (rep) are shown. (E) ChIP-seq with the indicated antibodies with average signal of read counts normalized to input shown across the gene body of known eggshell-protein-encoding genes (Tootle et al., 2011).
Source publication
Actin has been linked to processes spanning the whole gene expression cascade, from regulating specific transcription factors, such as myocardin-related transcription factor, to chromatin remodeling and RNA polymerase function. However, whether actin controls the transcription of only specific genes or has a global role in gene expression has remai...
Contexts in source publication
Context 1
... obtain a genome-wide view of actin-chromatin interactions, further ChIP-seq analysis of the w 1118 fly strain revealed actin on the promoters of essentially all transcribed genes together with Pol II S5P (Figure 2A). Peak calling confirmed the substantial overlap between actin and Pol II S5P binding sites ( Figure 2B). ...
Context 2
... obtain a genome-wide view of actin-chromatin interactions, further ChIP-seq analysis of the w 1118 fly strain revealed actin on the promoters of essentially all transcribed genes together with Pol II S5P (Figure 2A). Peak calling confirmed the substantial overlap between actin and Pol II S5P binding sites ( Figure 2B). However, detailed analysis showed that actin binds promoters slightly before the TSS and Pol II S5P enrichment ( Figure 2C), indicating that actin could be involved in transcriptional initiation, perhaps via pre-initiation complex formation, as suggested before ( Hofmann et al., 2004). ...
Context 3
... calling confirmed the substantial overlap between actin and Pol II S5P binding sites ( Figure 2B). However, detailed analysis showed that actin binds promoters slightly before the TSS and Pol II S5P enrichment ( Figure 2C), indicating that actin could be involved in transcriptional initiation, perhaps via pre-initiation complex formation, as suggested before ( Hofmann et al., 2004). ...
Context 4
... to the Act5C gene (Figure 1), actin was also found, together with Pol II S5P, on the gene bodies of certain genes (Figure 2A, genes at the bottom have highest expression). These included, for example, the highly transcribed chorion genes ( Figure 2D) involved in eggshell formation. ...
Context 5
... to the Act5C gene (Figure 1), actin was also found, together with Pol II S5P, on the gene bodies of certain genes (Figure 2A, genes at the bottom have highest expression). These included, for example, the highly transcribed chorion genes ( Figure 2D) involved in eggshell formation. On these genes actin is enriched more toward the transcription end site than the TSS ( Figure 2E). ...
Context 6
... included, for example, the highly transcribed chorion genes ( Figure 2D) involved in eggshell formation. On these genes actin is enriched more toward the transcription end site than the TSS ( Figure 2E). Notably, both actin antibodies produced a very similar binding pattern on chromatin (Figures 2A, 2B, 2D, and 2E). ...
Context 7
... these genes actin is enriched more toward the transcription end site than the TSS ( Figure 2E). Notably, both actin antibodies produced a very similar binding pattern on chromatin (Figures 2A, 2B, 2D, and 2E). This genome- wide analysis shows that actin interacts with most transcribed genes in Drosophila ovaries and that depending on the expression level of the gene, actin can be found both on the promoters and gene bodies. ...
Context 8
... the binding pattern of actin reflects its dual roles in transcription, both during transcription initiation and elongation, or whether the recruitment to gene bodies represents a specific requirement for actin upon high transcriptional activity, awaits further studies. An obvious candidate for recruiting actin to the genes is Pol II, which based on our ChIP-seq studies co-occupies most actin-binding sites (Figure 2), although not with exactly the same pattern. Other candidates include the different chromatin remodeling complexes containing actin (Kapoor and Shen, 2013), as well as the elongation factor P-TEFb ( Qi et al., 2011). ...
Similar publications
During the asymmetric divisions of Drosophila neuroblasts, the Par polarity complex cycles between the cytoplasm and an apical cortical domain that restricts differentiation factors to the basal cortex. We used rapid imaging of the full cell volume to uncover the dynamic steps that underlie transitions between neuroblast polarity states. Initially...
Citations
... Previous studies have indicated that SAF-A is involved in initial transcriptional regulation. Actin in the nucleus regulates transcription by remodeling chromatin, regulating transcription factor (TF) location, or binding to RNA polymerase (27)(28)(29)(30). Through extracellular vesicles derived from embryonic stem cells, SAF-A is transferred into human coronary artery endothelial cells to combine with actin. ...
As one member of the heterogeneous ribonucleoprotein (hnRNP) family, scaffold attachment factor A (SAF-A) or hnRNP U, is an abundant nuclear protein. With RNA and DNA binding activities, SAF-A has multiple functions. The present review focused on the biological structure and different roles of SAF-A and SAF-A-related diseases. It was found that SAF-A maintains the higher-order chromatin organization via RNA and DNA, and regulates transcription at the initiation and elongation stages. In addition to regulating pre-mRNA splicing, mRNA transportation and stabilization, SAF-A participates in double-strand breaks and mitosis repair. Therefore, the aberrant expression and mutation of SAF-A results in tumors and impaired neurodevelopment. Moreover, SAF-A may play a role in the anti-virus system. In conclusion, due to its essential biological functions, SAF-A may be a valuable clinical prediction factor or therapeutic target. Since the role of SAF-A in tumors and viral infections may be controversial, more animal experiments and clinical assays are needed.
... In particular, actin has been linked to many processes that regulate gene expression [43][44][45][46]. Actin interacts with essentially all transcribed genes in Drosophila ovaries [47], copurifies with all three eukaryotic RNA polymerases [44,45,48], and regulates the activity of specific transcription factors [49]. In addition to gene expression, actin is linked to DNA replication [50], DNA damage response [51][52][53][54][55], and long-range chromatin motion [56][57][58]. ...
... Nuclear export depends on binding to exportin 6 [62][63][64]. According to several reports, the nuclear import of actin depends on importin 9 [47,62,65]; however, a recent study indicated that multiple importins can transport actin into the nucleus in Drosophila [66]. Interestingly, actin, which has no NLS, is imported into the nucleus in complex with cofilin [67], which contains NLS [68,69]. ...
The troponin complex—consisting of three subunits: troponin C (TnC), cardiac troponin I (cTnI) and cardiac troponin T (cTnT)—plays a key role in the regulation of myocardial contraction. Troponins are preferentially localized in the cytoplasm and bind to myofibrils. However, numerous, albeit scattered, studies have shown the presence of troponins in the nuclei of muscle cells. There is increasing evidence that the nuclear localization of troponins may be functionally important, making troponins an important nuclear player in the pathogenesis of various diseases including cancer and myopathies. Further studies in this area could potentially lead to the development of treatments for certain pathologies. In this review, we collected and discussed recent data on the properties of non-canonically localized cardiac troponins, the molecular mechanisms leading to this non-canonical localization, and the possible functions or pathological effects of these non-canonically localized troponins.
... One of the essential functions of nuclear actin is its role in transcription regulation. For optimal transcription, the levels of actin inside the nucleus have to be controlled, as manipulating actin levels impairs transcription both in vitro and in cells (Dopie et al., 2012;Hu et al., 2004;Philimonenko et al., 2004;Sokolova et al., 2018). Decreased nuclear actin levels in response to laminin-111 and consequent PI3 kinase pathway attenuation leading to increased Exp6 activity have also been shown to destabilize Pol II and Pol III interactions with nuclear substructures, causing lower RNA synthesis rates and quiescence in mouse epithelial cells (Fiore et al., 2017;Spencer et al., 2011). ...
... Decreased nuclear actin levels in response to laminin-111 and consequent PI3 kinase pathway attenuation leading to increased Exp6 activity have also been shown to destabilize Pol II and Pol III interactions with nuclear substructures, causing lower RNA synthesis rates and quiescence in mouse epithelial cells (Fiore et al., 2017;Spencer et al., 2011). In Drosophila ovaries, actin and Pol II co-occupy promoter regions of most transcribed genes, as well as the gene bodies of highly transcribed genes (Sokolova et al., 2018). It is becoming clear that actin has functions throughout the transcription process. ...
... By using chromatin immunoprecipitation followed by deep-sequencing (ChIP-seq), we have demonstrated that actin interacts with all transcribed genes near transcription start sites (TSS) in Drosophila melanogaster ovaries. In addition, we showed that actin accumulates on gene bodies of highly transcribed genes required for egg shell formation during Drosophila oogenesis (Sokolova et al., 2018). Heat shock protein (hsp) genes encode chaperone proteins that are required to maintain proteostasis not only during proteotoxic stress, such as heat shock (HS), but also during normal conditions. ...
Nuclear actin has been demonstrated to be essential for optimal transcription, but the molecular mechanisms and direct binding partner for actin in the RNA polymerase complex have remained unknown. By using purified proteins in a variety of biochemical assays, we demonstrate a direct and specific interaction between monomeric actin and Cdk9, the kinase subunit of the positive transcription elongation factor b (P-TEFb) required for RNA polymerase II pause-release. This interaction efficiently prevents actin polymerization, is not dependent on kinase activity of Cdk9 and is not involved with releasing P-TEFb from its inhibitor 7SK snRNP complex. Supporting the specific role for actin in the elongation phase of transcription, chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) reveals that actin interacts with genes only upon their active transcription elongation. This study therefore provides novel insights into the mechanisms by which actin facilitates the transcription process.
... Induced strain in epidermal stem cells coincided with an increase in NMII, F-actin polymerisation, and Emerin at the nuclear envelope, forming a mechanosensory complex [44,45]. Emerin is present throughout the nucleus and links the nuclear lamina to constitutive heterochromatin however, strain causes Emerin in the nuclear interior to move the nuclear periphery reducing Lamin A/C interactions. ...
The importance of myosin motor protein is well-characterised within the cytoplasm and cytoskeleton. However, mounting evidence on four nuclear myosins highlights the central role these proteins have in maintaining genomic stability and gene expression. This review focuses on each of their critical roles in chromatin structure, chromosome translocation, transcription regulation, and DNA damage repair in terms of maintaining chromosome and chromatin integrity.
... Regulation of SRF activation ( Mouilleron et al., 2011;Olson and Nordheim, 2010;Posern and Treisman, 2006) Chromatin remodeling via SWI/SNF, SWR1, and INO80 association ( Szerlong et al., 2008;Kapoor et al., 2013) Association with RNA Polymerase I Association with RNA polymerase II Obrdlik et al., 2008;Sokolova et al., 2018) Association with RNA polymerase III ( Hu et al., 2004) Splicing and processing of pre-mRNA ( Viita et al., 2019) Export of mRNA to the cytoplasm (actin is a Modulation of the MRTF-A/SRF transcriptional activity (Baarlink et al., 2013;Lundquist et al., 2014;Plessner et al., 2015) Transcriptional modulation via RNA polymerase II clustering Export of mRNA to the cytoplasm, along which mRNP complexes can be transported ( Kimura et al., 2000) Translocation of malonylated mDia2 into cell nucleus leads to F-actin formation and increased chromosome accessibility ( Huang et al., 2022) β-actin associates with RNA polymerase III (Hu et al., 2004) Polymerization of β-actin in the nucleus is crucial for RNA polymerase I activity and rRNA synthesis. It is dependent on nuclear myosin 1 (NM1) (Almuzzaini et al., 2016) Modulation of gene expression clusters by β-actin through the Brg1 protein [a constituent of Brahma-associated factor (BAF) (SWI/SNF family) complex)] determines the cell identity (Xie et al., 2018a) with an example of genes cluster involved in neurogenesis (Xie et al., 2018b) Gata2 expression level is regulated by β-actin (Tondeleir et al., 2013) γ-actin regulates SRF signaling by interaction with MRTF-A (however, it cannot be excluded that β-actin also can interact with MRTF-A) (Lechuga et al., 2014; (continued on next page) E. Jeruzalska and A.J. Mazur associating with complexes like SWI/SNF, SWR1, and INO80, which contain Helicase-SANT-associated (HSA) domain that binds actin (Szerlong et al., 2008). ...
Uncontrolled cell proliferation leads to several pathologies, including cancer. Thus, this process must be tightly regulated. The cell cycle accounts for cell proliferation, and its progression is coordinated with changes in cell shape, for which cytoskeleton reorganization is responsible. Rearrangement of the cytoskeleton allows for its participation in the precise division of genetic material and cytokinesis. One of the main cytoskeletal components is filamentous actin-based structures. Mammalian cells have at least six actin paralogs, four of which are muscle-specific, while two, named β- and γ-actin, are abundantly present in all types of cells. This review summarizes the findings that establish the role of non-muscle actin paralogs in regulating cell cycle progression and proliferation. We discuss studies showing that the level of a given non-muscle actin paralog in a cell influences the cell's ability to progress through the cell cycle and, thus, proliferation. Moreover, we elaborate on the non-muscle actins' role in regulating gene transcription, interactions of actin paralogs with proteins involved in controlling cell proliferation, and the contribution of non-muscle actins to different structures in a dividing cell. The data cited in this review show that non-muscle actins regulate the cell cycle and proliferation through varying mechanisms. We point to the need for further studies addressing these mechanisms.
... Indeed, actin is a required cofactor for all three RNAPs, however the form of actin present in the different complex remains unclear Green et al., 2021). Data supports that monomeric actin is bound to gene promoters and mediates RNAPII recruitment (Sokolova et al., 2018), whether this is true for RNAPI remains unknown. Actin polymerization is required for RNAPI transcription (Percipalle, 2013). ...
Prostaglandins (PGs), locally acting lipid signals, regulate female reproduction, including oocyte development. However, the cellular mechanisms of PG action remain largely unknown. One cellular target of PG signaling is the nucleolus. Indeed, across organisms, loss of PGs results in misshapen nucleoli, and changes in nucleolar morphology are indicative of altered nucleolar function. A key role of the nucleolus is to transcribe ribosomal RNA (rRNA) to drive ribosomal biogenesis. Here we take advantage of the robust, in vivo system of Drosophila oogenesis to define the roles and downstream mechanisms whereby PGs regulate the nucleolus. We find that the altered nucleolar morphology due to PG loss is not due to reduced rRNA transcription. Instead, loss of PGs results in increased rRNA transcription and overall protein translation. PGs modulate these nucleolar functions by tightly regulating nuclear actin, which is enriched in the nucleolus. Specifically, we find that loss of PGs results in both increased nucleolar actin and changes in its form. Increasing nuclear actin, by either genetic loss of PG signaling or overexpression of nuclear targeted actin (NLS-actin), results in a round nucleolar morphology. Further, loss of PGs, overexpression of NLS-actin or loss of Exportin 6, all manipulations that increase nuclear actin levels, results in increased RNAPI-dependent transcription. Together these data reveal PGs carefully balance the level and forms of nuclear actin to control the level of nucleolar activity required for producing fertilization competent oocytes.
... Analyses in fission yeast, amphibians, and mammals have shown that actin interacts with the RNA Pol II transcriptional machinery at various points in mRNA biogenesis (Egly et al. 1984;Scheer et al. 1984;Hofmann et al. 2004;Kukalev et al. 2005;Mitsuzawa et al. 2005). Association of actin with Pol II has been reported to occur at constitutively expressed genes in both insects and mammals (McDonald et al. 2006;Ambrosino et al. 2010;Xu et al. 2010;Serebryannyy et al. 2016;Sokolova et al. 2018) as well as at cell type-specific genes (Al-Sayegh et al. 2020). Actin has been found within the promoter regions of Pol II-transcribed genes where it facilitates Pol II recruitment (Kukalev et al. 2005) and, as shown in cultured human cells, may also contribute to Pol II elongation by recruiting positive transcription elongation factor b (P-TEFb) to the carboxy-terminal domain of Pol II, leading to phosphorylation of Ser2 residues (Qi et al. 2011). ...
Nuclear actin has been implicated in dynamic chromatin rearrangements in diverse eukaryotes. In mammalian cells, it is required to reposition double-strand DNA breaks to enable homologous recombination repair and to enhance transcription by facilitating Pol II recruitment to gene promoters. In the yeast Saccharomyces cerevisiae, nuclear actin modulates interphase chromosome dynamics and is required to reposition the induced INO1 gene to the nuclear periphery. Here we have investigated the role of actin in driving intergenic interactions between Heat Shock Factor 1 (Hsf1)-regulated Heat Shock Protein (HSP) genes in budding yeast. These genes, dispersed on multiple chromosomes, dramatically reposition following exposure of cells to acute thermal stress, leading to their clustering within dynamic biomolecular condensates. Using an auxin-induced degradation strategy, we found that conditional depletion of nucleators of either linear or branched F-actin (Bni1/Bnr1 and Arp2, respectively) had little or no effect on heat shocked-induced HSP gene coalescence or transcription. In addition, we found that pretreatment of cells with latrunculin A (Lat-A), an inhibitor of both filamentous and monomeric actin, failed to affect intergenic interactions between activated HSP genes as well as their heat shock-induced intragenic looping and folding. Moreover, Lat-A pretreatment had little detectable effect on HSP gene expression at either RNA or protein levels. In notable contrast, we confirmed that repositioning of activated INO1 to the nuclear periphery and its proper expression do require actin. Collectively, our work suggests that transcriptional activation and 3D genome restructuring of thermally induced, Hsf1-regulated genes can occur in the absence of actin.
... genome-wide analysis in fly ovaries. For the first time, they showed that nuclear actin in physical conjunction with Pol II co-occupies the promoters associated with gene bodies of actively transcribed genes (Sokolova et al. 2018). Furthermore, by using immunoprecipitation, immunofluorescence, and glutathione S-transferase (GST) pull-down assay, Qi et al. and Hu et al. showed that nuclear actin directly interacts with Pol II subunits POLR2E and POLR2G, as well as Pol III subunits POLR3C, POLR2F, and POLR2H (Hu et al. 2004;Qi et al. 2011). ...
Actin is a highly conserved protein in mammals. The actin dynamics is regulated by actin-binding proteins and actin-related proteins. Nuclear actin and these regulatory proteins participate in multiple nuclear processes, including chromosome architecture organization, chromatin remodeling, transcription machinery regulation, and DNA repair. It is well known that the dysfunctions of these processes contribute to the development of cancer. Moreover, emerging evidence has shown that the deregulated actin dynamics is also related to cancer. This chapter discusses how the deregulation of nuclear actin dynamics contributes to tumorigenesis via such various nuclear events.KeywordsNuclear actinChromosome architectureChromatin remodelingBAF complexINO80 complexTranscription machineryRNA polymeraseDNA repairGene expressionCancer
... Rho1 has multiple functions but generally plays an important role in cell morphogenesis by regulating the cytoskeleton (Hall, 1998). It primarily has been implicated in actin regulation (Hall, 1998), which is itself important for insect oogenesis (Sokolova et al., 2018) but can also indirectly influence the microtubule network (Pimm and Henty-Ridilla, 2021). The regulation of Rho1 activity is complex (Denk-Lobnig and Martin, 2019), and multiple participating signaling pathways could transduce extracellular signals in the ovary into cytoskeletal reorganization of the eggs. ...
Reproduction involves the investment of resources into offspring. Although variation in reproductive effort often affects the number of offspring, adjustments of propagule size are also found in numerous species, including the Western honey bee, Apis mellifera. However, the proximate causes of these adjustments are insufficiently understood, especially in oviparous species with complex social organization in which adaptive evolution is shaped by kin selection. Here, we show in a series of experiments that queens predictably and reversibly increase egg size in small colonies and decrease egg size in large colonies, while their ovary size changes in the opposite direction. Additional results suggest that these effects cannot solely explained by egg laying rate and are due to the queens' perception of colony size. Egg size plasticity is associated with quantitative changes of 290 ovarian proteins, most of which relate to energy metabolism, protein transport, and cytoskeleton. Based on functional and network analyses, we further study the small GTPase Rho1 as a candidate regulator of egg size. Spatio-temporal expression analysis via RNAscope® and qPCR supports an important role of Rho1 in egg size determination, and subsequent RNAi-mediated gene knock-down confirmed that Rho1 has a major effect on egg size in honey bees. These results elucidate how the social environment of the honey bee colony may be translated into a specific cellular process to adjust maternal investment into eggs. It remains to be studied how widespread this mechanism is and whether it has consequences for population dynamics and epigenetic influences on offspring phenotype in honey bees and other species.
... Ipo9 (also known as RanBP9), the Drosophila orthologue of the vertebrate importin of actin, is encoded by the Ipo9 gene located on the third chromosome of the fruit fly. It was previously shown that the deletion of Ipo9 decreases nuclear actin levels (Sokolova et al., 2018;Palacios et al., 2021). Therefore, we tested whether the combination of an Ipo9 deficient background with NES-tagged actin expression can significantly reduce nuclear actin level and, as a consequence, viability. ...
... Cas, Dcas, l(2)k03902, CAS/ CSE1 segregation protein CSE1L (Kimura and Imamoto, 2014;Lippai et al., 2000) Fs (2) IPO7 (Kimura and Imamoto, 2014;Lippai et al., 2000) Ipo9 CG5252 Importin 9 RanBP9 IPO9 (Sokolova et al., 2018;Palacios et al., 2021) Impβ11 CG33139 Importin beta11 RanBP11, importin-β11, Imp11, CG8212 IPO11 (Kimura and Imamoto, 2014;Lippai et al., 2000;Boeynaems et al., 2016;Mosca and Schwarz, 2010) cdm CG7212 cadmus importin 13, sd-5, Imp13, cdm IPO13 (Kimura and Imamoto, 2014) emb CG13387 embargoed Crm1, dCRM1, Exportin, XPO1, l(2) k16715 XPO1 (Kimura and Imamoto, 2014;Lippai et al., 2000) Ranbp21 CG12234 RanBP21 Exp5, Exportin-5, Exp-5, Exportin 5 XPO5 (Lippai et al., 2000) CG8219 CG8219 TNPO1 (Lippai et al., 2000) Tnpo CG7398 Transportin Trn, dTRN, Imp beta2 TNPO1, TNPO2 (Lippai et al., 2000;Boeynaems et al., 2016) Tnpo-SR CG2848 Transportin-Serine/ Arginine rich Trn-SR, TNPO3 TNPO3 (Lippai et al., 2000) Ntf-2 CG1740 Nuclear transport factor-2 DNTF-2, Ntf2, l(1)G0428, l(1)G0086, l (1) ...
... These observations strongly suggest that tightly regulated, highly effective active import mechanism is the primary mean of actin's nuclear entry. Until recently, only a single actin importin, Ipo9, had been identified in mammalian cells (Dopie et al., 2012), which had also been confirmed in Drosophila (Sokolova et al., 2018;Palacios et al., 2021). Interestingly, despite the fact that actin is not the only cargo of Ipo9-in mice it transports ribosomal proteins, histone H2B and heat shock protein hsp27 (Jäkel et al., 2002)homozygous null mutant flies are viable with no phenotypic change. ...
Actin, as an ancient and fundamental protein, participates in various cytoplasmic as well as nuclear functions in eukaryotic cells. Based on its manifold tasks in the nucleus, it is a reasonable assumption that the nuclear presence of actin is essential for the cell, and consequently, its nuclear localization is ensured by a robust system. However, today only a single nuclear import and a single nuclear export pathway is known which maintain the dynamic balance between cytoplasmic and nuclear actin pools. In our work, we tested the robustness of the nuclear import of actin, and investigated whether the perturbations of nuclear localization affect the viability of the whole organism. For this aim, we generated a genetic system in Drosophila, in which we rescued the lethal phenotype of the null mutation of the Actin5C gene with transgenes that express different derivatives of actin, including a Nuclear Export Signal (NES)-tagged isoform which ensures forced nuclear export of the protein. We also disrupted the SUMOylation site of actin, suggested earlier to be responsible for nuclear retention, and eliminated the activity of the single nuclear import factor dedicated to actin. We found that, individually, none of the above mentioned manipulations led to a notable reduction in nuclear actin levels and thus, fully rescued lethality. However, the NES tagging of actin, together with the knock out of its importin, significantly reduced the amount of nuclear actin and induced lethality, confirming that the presence of actin in the nucleus is essential, and thereby, over-secured. Supporting this, we identified novel nuclear importins specific to actin, which sheds light on the mechanism behind the robustness of nuclear localization of actin, and supports the idea of essentiality of its nuclear functions.
